SI2970332T1 - Chemical entities - Google Patents

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SI2970332T1
SI2970332T1 SI201430698T SI201430698T SI2970332T1 SI 2970332 T1 SI2970332 T1 SI 2970332T1 SI 201430698 T SI201430698 T SI 201430698T SI 201430698 T SI201430698 T SI 201430698T SI 2970332 T1 SI2970332 T1 SI 2970332T1
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alkyl
optionally substituted
halo
cycloalkyl
chemical entity
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Fernandez Joaquin Pastor
Ruiz Oscar Fernandez-Capetillo
Gonzalez Sonia Martinez
Aparicio Carmen Blanco
Ferreira Maria Del Rosario Rico
Lazaro Luis Ignacio Toledo
Aristegui Sonsoles Rodriguez
Costa Matilde Murga
Busto Carmen Varela
Contreras Andres Joaquin Lopez
Oliver Renner
Soler Maria Nieto
Munoz David Alvaro Cebrian
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Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/14—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Provided are chemical entities selected from compounds of formula (I), wherein R1, R2 and m have meanings given in the description, and pharmaceutically acceptable salts, solvates and stereoisomers thereof, which are inhibitors of ATR and are potentially useful in the treatment of cancer. Further provided are pharmaceutical compositions of the chemical entities, combination products containing the chemical entities, the use of the compositions as therapeutic agents, and methods of treatment using these compositions.

Description

Original document published without description

Claims (15)

Kemijske entitete Patentni zahtevkiChemical entities Patent claims 1. Kemijska entiteta, izbrana izmed spojin s formulo (I) kjerA chemical entity selected from compounds of formula (I) wherein Ri predstavlja biciklični heteroaril, izbran iz skupine, ki jo sestavljajo indazolil, indolil, benzimidazolil in pirolopiridinil; R2 je izbran izmed NR3SO2R3, alkila in cikloalkila; kjer je R3, ob vsakem pojavljanju, neodvisno izbran izmed H, alkila, po izbiri substituiranega z 1,2 ali 3 halo atomi, cikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, in heterocikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi; in m je 1 ali 2; alkil je raven nasičen ogljikovodik z do 10 atomi ogljika (CrCio) ali razvejen nasičen ogljikovodik z med 3 in 10 atomi ogljika (C3-C10); cikloalkil je mono- ali bi-ciklični nasičen C3-C10 ogljikovodik, ki je po izbiri lahko pripojen na arilno skupino; ali je cikloalkil adamantil; heterocikloalkil je C-vezan ali N-vezan 3-10 členski nasičen mono- ali bi-ciklični obroč, ki vsebuje 1, 2, 3 ali 4 obročne heteroatome, neodvisno izbrane izmed N, S in O, kjer je N ali S atom v obroču lahko substituiran s kisikom, da tvori N-oksid, sulfoksid ali sulfonsko skupino; aril je fenil, bifenil ali naftil; in heteroaril je 5, 6, 9 ali 10, 12, 13 ali 14 členski mono-, bi- ali tri-ciklični aromatski obroč, ki lahko vsebuje 1, 2, 3 ali 4 obročne heteroatome, neodvisno izbrane izmed N, S in O; kjer je, kadar R2 predstavlja alkil ali cikloalkil, navedeni alkil ali cikloalkil substituiran z vsaj enim substituentom, izbranim izmed (NR^nSC^Rt, kjer je n 0 ali 1, OH in CN; in je navedeni alkil ali cikloalkil nadalje po izbiri substituiran z 1 ali 2 substituentoma, neodvisno izbranima izmed halo, CN, COOR4, CF3, (Ci-C6)alkila, po izbiri substituiranega z 1,2 ali 3 halo atomi, cikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, in 0(Ci-C6)alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, ali z 2 substituentoma na enem atomu, ki skupaj z atomom, na katerega sta vezana, tvorijo ciklično strukturo, izbrano izmed cikloalkila in heterocikloalkila, po izbiri substituiranega za 1, 2 ali 3 skupinami, izbranimi izmed halo, C1-C4 alkila, C(0)CrC4 alkila in C(0)0-Ci-C4 alkila; kadar je R3 izbran izmed alkila, cikloalkila in heterocikloalkila, potem so navedeni alkil, heterocikloalkil in cikloalkil, ob vsakem pojavljanju, lahko po izbiri substituirani z 1, 2, 3,4 ali 5 substituenti, kjer so substituenti neodvisno izbrani izmed halo, OH, CN, COOR4, CF3, NR4R4, NR4COR4, (NR4)nS02R4, kjer je n 0 ali 1, alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, cikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, O-alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, in kjer lahko dva substituenta na enem atomu skupaj z atomom, na katerega sta vezana, tvorita ciklično strukturo, izbrano izmed cikloalkila in heterocikloalkila, po izbiri substituiranega z 1, 2 ali 3 skupinami, izbranimi izmed halo, C(0)Ci-C4 alkila, C(0)0-(Ci-C4 alkila) in C1-C4 alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi; i vsaka biciklična heteroarilna skupina, predstavljena z Ri, je, ob vsakem pojavljanju, lahko po izbiri substituirana z 1, 2, 3, 4 ali 5 substituenti, neodvisno izbranimi izmed halo, OH, CN, COOR4, CF3, NR4R4, NR4COR4, (NR4)nS02R4, kjer je n 0 ali 1, NHR5, alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, O-alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, cikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, in heterocikloalkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi; R» je, ob vsakem pojavljanju, neodvisno izbran izmed H, alkila, arila, heteroarila, cikloalkila in heterocikloalkila, kjer so alkil, aril, heteroaril, cikloalkil in heterocikloalkil po izbiri substituirani z 1, 2 ali 3 substituenti, izbranimi izmed halo, alkila, O-alkila, N(Ci-C4alkila)2, N(C i-C4alkil)COC i-C4alkila, ali R» skupine skupaj z atomom(i), na katerega(katere) so vezane, tvorijo heterocikloalkil, po izbiri substituiran z 1, 2 ali 3 halo atomi, ali kadar je substituent, ki obsega R4 skupino, prisoten na alkilu, cikloalkilu ali heterocikloalkilu, lahko R4 skupina skupaj s substituentom, na tem alkilu, cikloalkilu ali heterocikloalkilu, tvori heterocikloalkil, po izbiri substituiran z 1, 2 ali 3 halo atomi; in R5 je neodvisno izbran izmed COalkila, COarila ali COheteroarila; in njene farmacevtsko sprejemljive soli, solvati in stereoizomeri.R1 represents a bicyclic heteroaryl selected from the group consisting of indazolyl, indolyl, benzimidazolyl and pyrrolopyridinyl; R2 is selected from NR3SO2R3, alkyl and cycloalkyl; wherein R 3 is independently selected from H, alkyl optionally substituted with 1,2 or 3 halo atoms, cycloalkyl optionally substituted with 1, 2 or 3 halo atoms, and heterocycloalkyl optionally substituted with 1, 2 or 3 halo atoms; and m is 1 or 2; alkyl is a linear saturated hydrocarbon having up to 10 carbon atoms (C 1 -C 10) or a branched saturated hydrocarbon having from 3 to 10 carbon atoms (C 3 -C 10); cycloalkyl is a mono- or bi-cyclic saturated C3-C10 hydrocarbon optionally attached to the aryl group; or cycloalkyl is adamantyl; heterocycloalkyl is a C-linked or N-linked 3-10 membered saturated mono- or bi-cyclic ring containing 1, 2, 3 or 4 ring heteroatoms independently selected from N, S and O, wherein N or S is the atom in the ring may be substituted with oxygen to form an N-oxide, a sulfoxide or a sulfone group; aryl is phenyl, biphenyl or naphthyl; and heteroaryl is a 5, 6, 9 or 10, 12, 13 or 14 membered mono-, bi- or tri-cyclic aromatic ring which may contain 1, 2, 3 or 4 ring heteroatoms independently selected from N, S and O ; wherein when R 2 is alkyl or cycloalkyl, said alkyl or cycloalkyl is substituted with at least one substituent selected from (NR 6) n R 6, wherein n is 0 or 1, OH and CN, and said alkyl or cycloalkyl is further optionally substituted with 1 or 2 substituents independently selected from halo, CN, COOR 4, CF 3, (C 1 -C 6) alkyl optionally substituted with 1,2 or 3 halo atoms, cycloalkyl optionally substituted with 1, 2 or 3 halo atoms, and O (C 1 -C 6) alkyl optionally substituted with 1, 2 or 3 halo atoms, or with 2 substituents on one atom which, together with the atom to which they are attached, form a cyclic structure selected from cycloalkyl and heterocycloalkyl, after optionally substituted by 1, 2 or 3 groups selected from halo, C 1 -C 4 alkyl, C (O) C 1 -C 4 alkyl and C (O) O-C 1 -C 4 alkyl; when R 3 is selected from alkyl, cycloalkyl and heterocycloalkyl, said alkyl, heterocycloalkyl and cycloalkyl, at each occurrence, may be optionally substituted with 1, 2, 3, 4 or 5 wherein the substituents are independently selected from halo, OH, CN, COOR4, CF3, NR4R4, NR4COR4, (NR4) nSO2R4, wherein n is 0 or 1, alkyl optionally substituted with 1, 2 or 3 halo atoms, cycloalkyl, optionally substituted with 1, 2 or 3 halo atoms, O-alkyl optionally substituted with 1, 2 or 3 halo atoms, and wherein the two substituents on one atom together with the atom to which they are attached form a cyclic structure selected cycloalkyl and heterocycloalkyl optionally substituted with 1, 2 or 3 groups selected from halo, C (O) C 1 -C 4 alkyl, C (O) O- (C 1 -C 4 alkyl) and C 1 -C 4 alkyl, optionally substituted with 1, 2 or 3 halo atoms; and each bicyclic heteroaryl group represented by R1, at each occurrence, may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halo, OH, CN, COOR4, CF3, NR4R4, NR4COR4, ( NR4) nSO2R4, wherein n is 0 or 1, NHR5, alkyl optionally substituted with 1, 2 or 3 halo atoms, O-alkyl optionally substituted with 1, 2 or 3 halo atoms, cycloalkyl optionally substituted with 1 , 2 or 3 halo atoms, and heterocycloalkyl optionally substituted with 1, 2 or 3 halo atoms; R @ 2 at each occurrence is independently selected from H, alkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl, wherein alkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl are optionally substituted with 1, 2 or 3 substituents selected from halo, alkyl , O-alkyl, N (C 1 -C 4 alkyl) 2, N (C 1 -C 4 alkyl) COC 1 -C 4 alkyl, or R 5 groups together with the atom (i) to which they are attached form heterocycloalkyl, with 1, 2 or 3 halo atoms, or when a substituent comprising the R 4 group is present on alkyl, cycloalkyl or heterocycloalkyl, the R 4 group together with the substituent on this alkyl, cycloalkyl or heterocycloalkyl forms heterocycloalkyl optionally substituted with 1 , 2 or 3 halo atoms; and R5 is independently selected from COalkyl, COaryl or COheteroaryl; and pharmaceutically acceptable salts, solvates and stereoisomers thereof. 2. Kemijska entiteta po zahtevku 1, kjer jeThe chemical entity of claim 1, wherein Ri izbran izmed kjer R$ je izbran izmed halo in H; R.7, Rg in so vsak neodvisno izbrani izmed H; halo; CN; Ri0; in ORio; kjer je Rio (Ci-C6)alkil, po izbiri substituiran z 1,2 ali 3 halo atomi; Rn je izbran izmed H, Ri0, NR4R4 in NR4COR4; kjer je R4, ob vsakem pojavljanju, neodvisno izbran izmed H ali alkila, po izbiri substituiranega z 1, 2 ali 3 halo atomi, ali R4 skupine skupaj z atomom(i), na katerega(katere) so vezane, tvorijo heterocikloalkil, po izbiri substituiran z 1, 2 ali 3 halo atomi; in R12 je izbran izmed H, halo, ORi0 ali Rio.R 1 is selected from where R 8 is selected from halo and H; R 7, R 8 and are each independently selected from H; halo; CN; Ri0; and OR10; wherein R 10 is (C 1 -C 6) alkyl optionally substituted with 1,2 or 3 halo atoms; R11 is selected from H, R10, NR4R4 and NR4COR4; wherein at each occurrence R4 is independently selected from H or alkyl optionally substituted with 1, 2 or 3 halo atoms, or R4 groups together with the atom (i) to which they are attached form heterocycloalkyl, optionally substituted with 1, 2 or 3 halo atoms; and R12 is selected from H, halo, OR10 or R10. 3. Kemijska entiteta po zahtevku 2, kjer: (i) Roje izbran izmed H in halo; R7, R8 in R9 so izbrani izmed H, halo, CN, 0(Ci-C6)alkila in (Ci-C6)alkila, po izbiri substituiranega z enim ali več halo atomi; Rn je izbran izmed H, (Ci-C6)alkila, NR4R4 in NR4COR4; in R12 je izbran izmed H, halo, (Ci-C6)alkila in 0(CrC6)alkila; (ii) Ro, R7, R$, R9 in Ri2 so H; in Rn je izbran izmed (Ci-C6)alkila, NR4R4 in NR4COR4; (iii) Ro, Rg, R9, Rn in RJ2 so H; in R7 je izbran izmed halo, CN, 0(Ci-Co)alkila in (Ci-Ce)alkila, po izbiri substituiranega z 1,2 ali 3 halo atomi; ali (iv) Ro, R7, R«, R9, Ru in Ri2 so H.The chemical entity of claim 2, wherein: (i) the roe is selected from H and halo; R7, R8 and R9 are selected from H, halo, CN, O (C1-C6) alkyl and (C1-C6) alkyl optionally substituted with one or more halo atoms; R11 is selected from H, (C1-C6) alkyl, NR4R4 and NR4COR4; and R12 is selected from H, halo, (C1-C6) alkyl and O (C1-C6) alkyl; (ii) Ro, R 7, R 8, R 9 and R 12 are H; and R11 is selected from (C1-C6) alkyl, NR4R4 and NR4COR4; (iii) Ro, R8, R9, R11 and R12 are H; and R 7 is selected from halo, CN, O (C 1 -C 10) alkyl and (C 1 -C 6) alkyl optionally substituted with 1,2 or 3 halo atoms; or (iv) Ro, R7, R11, R9, Ru and Ri2 are H. 4. Kemijska entiteta po zahtevku 1, kjer: R2 je (CH2)pC(Ri3)2(CH2)qQ, kjer je Q (NR4)nS02R4, OH ali CN, kjer sta p in q neodvisno 0,1 ali 2, in kjer (i) R13 je, ob vsakem pojavljanju, neodvisno izbran iz skupine, ki jo sestavljajo H in (CpC^alkil, ali (ii) en R13 je izbran iz skupine, ki jo sestavljajo H in (CpC^alkil, ali drugi R13, skupaj z R4, če je prisoten, tvori 3-6 členski heterocikloalkil, po izbiri substituiran z 1, 2 ali 3 halo atomi, ali (iii) R13 skupini skupaj z ogljikom, na katerega sta vezani, tvorita ciklično strukturo, izbrano izmed (C3-C6)cikloalkila in 3-6 členskega heterocikloalkila, po izbiri substituiranega z 1, 2 ali 3 skupinami, izbranimi izmed halo, C1-C4 alkila, C(0)Ci-C4 alkila in C(0)0-Ci-C4 alkila.The chemical entity of claim 1 wherein: R2 is (CH2) pC (R13) 2 (CH2) qQ, wherein Q is (NR4) nSO2R4, OH or CN, wherein p and q are independently 0, 1 or 2, and wherein (i) R 13 is, at each occurrence, independently selected from the group consisting of H and (C 1 -C 4) alkyl, or (ii) one R 13 is selected from the group consisting of H and (C 1 -C 4) alkyl or the other R 13 , together with R4, if present, forms a 3-6 membered heterocycloalkyl optionally substituted with 1, 2 or 3 halo atoms, or (iii) R13 together with the carbon to which they are attached form a cyclic structure selected from ( C3-C6) cycloalkyl and 3-6 membered heterocycloalkyl optionally substituted with 1, 2 or 3 groups selected from halo, C1-C4 alkyl, C (O) C1-C4 alkyl and C (O) O-C1-C4 alkyl. 5. Kemijska entiteta po zahtevku 4, kjer sta obe R13 skupini H, kjer sta obe R43 skupini metil ali kjer Rj3 skupini skupaj z ogljikom, na katerega sta vezani, tvorita ciklopropanil, ciklobutil, tetrahidropiranil, piperidinil, N-etoksikarbonilpiperidinil ali 7V-metilpiperidinil; po izbiri, kjer je Q SO2R4.The chemical entity of claim 4, wherein both R 13 are H, wherein both R 43 are methyl, or R 1 3 together with the carbon to which they are attached form cyclopropanyl, cyclobutyl, tetrahydropyranyl, piperidinyl, N-ethoxycarbonylpiperidinyl or 7V-methylpiperidinyl ; optionally, wherein Q is SO 2 R 4. 6. Kemijska entiteta po katerem koli predhodnem zahtevku, kjer kadar je m 1, je obvezni kiralni center v kemijski entiteti s formulo (I) v (S) konfiguraciji in kadar je m 2, je obvezni kiralni center v kemijski entiteti s formulo (I) v (R) konfiguraciji.A chemical entity according to any preceding claim wherein, when m is 1, the mandatory chiral center in the chemical entity of formula (I) in the (S) configuration and when m 2 is a mandatory chiral center in the chemical entity of formula (I ) in the (R) configuration. 7. Kemijska entiteta po zahtevku 1, izbrana iz skupine, ki jo sestavljajo:The chemical entity of claim 1, selected from the group consisting of: in njene farmacevtsko sprejemljive soli, solvati in stereoizomeri.and pharmaceutically acceptable salts, solvates and stereoisomers thereof. 8. Kemijska entiteta, izbrana iz skupine, ki jo sestavljajo:A chemical entity selected from the group consisting of: in njene farmacevtsko sprejemljive soli, solvati in stereoizomeri.and pharmaceutically acceptable salts, solvates and stereoisomers thereof. 9. Farmacevtski sestavek, ki obsega kemijsko entiteto po katerem koli od zahtevkov od 1 do 8 in farmacevtsko sprejemljiv nosilec, razredčilo ali ekscipient.A pharmaceutical composition comprising a chemical entity according to any one of claims 1 to 8 and a pharmaceutically acceptable carrier, diluent or excipient. 10. Kemijska entiteta po katerem koli od zahtevkov od 1 do 8 za uporabo v medicini.A chemical entity according to any one of claims 1 to 8 for use in medicine. 11. Kemijska entiteta po katerem koli od zahtevkov od 1 do 8 za uporabo v postopku zdravljenja bolezni ali stanja, pri katerem je implicirana aktivnost ATR.A chemical entity according to any one of claims 1 to 8 for use in a method of treating a disease or condition in which an ATR activity is implicated. 12. Uporaba kemijske entitete po katerem koli od zahtevkov od 1 do 8 v izdelavi zdravila za zdravljenje bolezni ali stanja, pri katerem je implicirana aktivnost ATR.Use of a chemical entity according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of a disease or condition in which an ATR activity is implicated. 13. Kemijska entiteta po zahtevku 11 ali uporaba po zahtevku 12, kjer je bolezen ali stanje, pri katerem je implicirana aktivnost ATR, bolezen ali stanje, povezano s povečano proliferacijo, kot je rak.A chemical entity according to claim 11 or use according to claim 12, wherein the disease or condition in which the ATR activity is implicated is a disease or condition associated with an increased proliferation such as cancer. 14. Kemijska entiteta za uporabo po zahtevku 13, kjer je bolezen ali stanje, pri katerem je implicirana aktivnost ATR, endometrijski rak, rak kolona ali rak želodca.A chemical entity for use according to claim 13, wherein the disease or condition in which the ATR activity is implicated is endometrial cancer, colon cancer, or gastric cancer. 15. Kombinacijski proizvod, ki obsega: (A) kemijsko entiteto po katerem koli od zahtevkov od 1 do 8; in (B) drugo terapevtsko sredstvo, ki je uporabno v zdravljenju raka in/ali proliferativne bolezni, kjer je vsaka od komponent (A) in (B) formulirana v zmesi s farmacevtsko sprejemljivim adjuvansom, razredčilom ali nosilcem.A combination product comprising: (A) a chemical entity according to any one of claims 1 to 8; and (B) a second therapeutic agent useful in the treatment of cancer and / or proliferative disease, wherein each of the components (A) and (B) is formulated in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
SI201430698T 2013-03-15 2014-03-14 Chemical entities SI2970332T1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
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